Alexandr Poprach, Radek Lakomý
Jana Katolická, Sabina Svobodová, Jiří Vaníček, Pavlína Prosecká
Libor Staněk, Robert Gürlich, Petra Tesařová
Lenka Jakubíková, Jana Špeldová, Marcela Tomíšková, Jana Skřičková
New findings in the pathogenesis of metastatic renal cell carcinoma (mRCC) led to the development of VEGF and mTOR pathway inhibitors over the last 20 years. Despite the prolongation of survival achieved with targeted treatment, almost all patients eventually develop resistance. Only new therapeutic strategies can result in a further substantial improvement in survival, or even achieve cure in patients with mRCC. Nivolumab, an inhibitor of the PD-1 immune checkpoint, was the first of the novel immunological agents to be successfully tested in a randomised trial. Regimens in which PD-1 or PD-L1 inhibitors are combined with other immunological drugs or tyrosine kinase inhibitors of angiogenesis are currrently being tested in preclinical and clinical studies seeking to build on the success of nivolumab.
Disseminated renal cell carcinoma is incurable. In the second line of palliative treatment, we can now usually use everolimus or axitinib. The breakthrough in treatment in the second line is the results of Phase 3 studies (METEOR - Cabozantinib study and CHECKMATE 025 - Nivolumab study). Nivolumab prolonged overall survival when compared to everolimus, the time to progression was the same, but cabozantinib prolonged both progression and overall survival when compared to everolimus. Cabozantinib is an oral inhibitor of many receptor tyrosine kinases. Unlike other commonly used multi-enzyme inhibitors that are used in renal cell carcinoma, it also inhibits MET and AXL protein kinases. These are more pronounced in patients after sunitinib treatment and also in patients in a poor prognostic group. In this review we will look at cabozantinib - the mechanism of its effect, the characteristics of the drug and the recent results of the studies.
Targeted treatment is currently a standard therapeutic method for metastatic clear cell renal carcinoma. Cabozantinib is an oral tyrosine kinase inhibitor including MET, VEGFR, and AXL. In a randomized phase III METEOR study, prolongation of survival in patients following prior VEGFR treatment with tyrosine kinase inhibitors has been demonstrated.
The epidermal growth factor receptor (EGFR) plays an important role in the development and progression of human epithelial carcinomas, including non-small cell lung cancer (NSCLC). Activation of the EGFR pathway promotes tumor growth and progression, stimulates tumor cell proliferation, angiogenic factors, invasion and metastasis, and suppresses apoptosis. Several studies have confirmed the predictive role of activation mutations in EGFR exons 19 and 21 for NSCLC. Their presence is clearly associated with higher efficacy of EGFR tyrosine kinase inhibitors (EGFR TKI). We have reversible EGFR TKI of the 1st generation erlotinib and gefitinib, the irreversible EGFR TKI 2nd generation afatinib, and also the already irreversible EGFR TKI 3rd generation osimertinib, the indication of which is above all the proven T790M mutation.
Relapsed/refractory adult acute lymphoblastic leukemia is a serious clinical issue poorly manageable by the standard of care chemotherapy. Too many of these patients do not achieve a remission and survive only several months. Blinatumomab is a new promising immunotherapy drug targeting CD19 antigen present on a vast majority of B lineage adult acute lymphoblastic leukemia cells. Clinical trials have proven it to induce a remission more frequently compared to the standard treatment and thus such patients can proceed to an allogeneic transplant and take their chance towards a permanent cure. Adverse events are usually moderate and easily manageable. The major limiting factor for its use in a broader spectrum of patients is a very high market price, making blinatumomab the most expensive cancer drug on the market.
Malignant tumours of the thyroid gland are relatively rare, their incidence is, however, permanently escalating. The most frequent among them is the differentiated thyroid cancer: papillary, follicular and Hurthle cell carcinomas. In the initial stages the prognosis of these tumours is excellent. Nevertheless, only few therapeutic modalities are available for advanced or metastatic disease. In the last decade, a better understanding of the molecular events involved in the thyroid cancer has led to introduction of new targeted agents for the management of advanced radioiodine-refractory disease. Multikinase inhibitors are able to block pathways involved in the proliferation, invasion, and neoangiogenesis of thyroid cancer. Their effectiveness was proved in several clinical placebo-controlled clinical trials. The purpose of this paper is a special focus on lenvatinib, a multikinase inhibitor.
Gastrointestinal stromal tumor was one of the first solid tumors, where previous palliative treatment with chemotherapy was completely replaced by biological treatment. Imatinib mesylate was significant turning point for patients, imatinib against previous treatments significantly prolonged survival in metastatic gastrointestinal stromal tumor cases and reduced recurrence rates and prolonged survival in patients following radical resections of risk groups of patients with gastrointestinal stromal tumors. After imatinib failure, preparations such as sunitinib and regorafenib are available. In recent years, new molecules for gastrointestinal stromal tumors treatment are under research and the dependence of therapy effect on c-Kit receptor mutation status and the serum concentration of imatinib is being investigated.
Localization of right/left side of colorectal carcinomas and its importance in prognosis and therapy disease
Colorectal cancer is a serious global disease with high incidence and mortality. With the development of diagnostics in molecular oncology, we try to find predictive and prognostic factors in the search for the most effective therapy. At present, it is a molecular testing of tumors prior to considering anti-EGFR therapy. The latest available studies, however, show that the carcinoma located in the right part of the intestine has a lower sensitivity and response to this treatment than the carcinoma on its left. The essence of this phenomenon remains a question. If these changes can be identified, they can be used to optimize therapy.
Currently the most children with cancer can be cured with standard therapy (surgery, chemotherapy, radiotherapy). The only limiting factor is its severe acute toxicity and late adverse events. In pediatric oncology immunotherapy has some delay, but the initial clinical trials of immunotherapy show a good tolerance and promising results, specially in the setting of refractory or recurrent high-risk tumors. In this article we will discuss a current situation in pediatric oncology, what immunotherapies are being tested in the clinical practice, from monoclonal antibodies, check-point inhibitors to tumor vaccines, chimeric antigene receptors, cytokines and innate immunity.
Trifluridin/tipiracil (Lonsurf, TAS-102) represents a new option for the treatment of patients with metastatic colorectal cancer (mCRC) on the 3rd and upper line. It reduces the risk of death by 31% compared to placebo (overall survival, OS 71 vs. 5.3 months, hazard ratio [HR], 95% CI 0.68 [0.58-0.81], p < 0.001), and a risk of disease progression by 52% compared to placebo (progression free survival [PFS] 2.0 vs. 1.7 months, p < 0.001), confirmed by the phase III clinical trial RECOURSE . The benefit was observed in all subgroups of patients regardless of the KRAS mutation, refractoriness to 5-fluorouracil in previous lines. The following case study confirms the benefit of the combination of trifluridine/tipiracil in a pre-treated patient with mCRC.
The authors of the first part of the article summarize the current therapeutic results of nivolumab in both squamous and non-squamous lung cancer, as well as the safety profile of this type of immunotherapy, including recommendations for prevention and measures for the occurrence of side effects. In particular, adverse events, particularly weakness and exhaustion, were reported in two selected patients who experienced a severe fatigue with the need for permanent discontinuation of treatment immediately after initiation of treatment with nivolumab, but two months after the last dose of immunotherapy, partial healing response that lasted for one year in both patients was observed.
Treatment with peroral vinorelbine in 98‑year old patient with locally advanced breast carcinoma – case report
Locally advanced breast carcinoma is generally treated with systemic therapy prior to locoregional surgery and/or radiotherapy. Antracycline and taxane based chemotherapy is the method of choice in the neoadjuvant treatment, with considerable toxicity that make the treatment impossible in elderly and frail patients. On the other hand, peroral vinorelbine is generally well tolerated in older women with metastatic breast carcinoma, on the basis of prospective trials and long-term clinical practice. This is a case report describing excellent effect and tolerance to long-term vinorelbine chemotherapy in very old and frail woman with chemonaive locally advanced breast carcinoma. Long-term treatment with lasting and re-inducible response and good quality of life can be achieved by this accessible and inexpensive approach.